Alloxan induced neuroprotection in cultured cortical neurons exposed to oxygen glucose deprivation is mediated through alterations in synaptic function

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DOIResolve DOI: http://doi.org/10.1093/glycob/cwq137
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TypeAbstract
Proceedings titleGlycobiology
ConferenceAnnual Meeting of the Society for Glycobiology (SFG 2010), November 7-10, 2010, St. Petersburg, Florida, USA
ISSN0959-6658
1460-2423
Volume20
Issue11
Pages14511451; # of pages: 1
AbstractProtein O-GlcNAcation is a stress-induced post-translational modification of intracellular proteins. A variety of neuronal proteins have been shown to harbour O-GlcNAc modifications, which are dynamically regulated by two enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). We examined the effect of blocking OGT and OGA on oxygen glucose deprivation (OGD) induced cell death in primary cortical neurons. Western blot analysis revealed that OGD did not produce a pronounced effect of O-GlcNAcation. However, OGA inhibition with Pugnac induced a marked increase in protein O-GlcNAcation but did not impart a neuroprotective effect against OGD. OGT inhibition with alloxan produced a moderate decrease in protein O-GlcNAcation, but produced a significant neuroprotective effect against OGD and NMDA toxicity. This neuroprotective effect was not associated with inhibition of NMDA channel activity, as alloxan did not inhibit NMDA-stimulated Ca++ currents. Furthermore, alloxan did not inhibit either staurosporin- or H2O2-induced cell death. Lastly, multi-electrode array (MEA) analysis of cultured neurons demonstrated that alloxan and Pugnac treatment modulated synaptic signalling. This study demonstrates that protein O-GlcNAcation modulates synaptic function, and that alterations in synaptic responsiveness are responsible for alloxanmediated neuroprotection.
Publication date
PublisherOxford University Press
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedYes
NPARC number17481801
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Record identifierb6f21c6e-6753-4207-aca3-28d847dec078
Record created2011-04-08
Record modified2016-08-22
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